Abstract
Pharmacometabolomics is a useful tool to identify biomarkers that can assess and predict response after drug administration. The primary purpose of pharmacometabolomics is to better understand the mechanisms and pathways of a drug by searching endogenous metabolites that have significantly changed after drug administration. DA-9701, a prokinetic agent, consists of Pharbitis seed and Corydalis tube extract and it is known to improve the gastrointestinal motility. Although the overall mechanism of action of DA-9701 remains unclear, its active ingredients, corydaline and chlorogenic acid, act as a 5-HT3 and D2 receptor antagonist and 5-HT4 receptor agonist. To determine the significant metabolites after the administration of DA-9701, a qualitative analysis was carried out using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometer followed by a multivariate analysis. Seven candidates were selected and a statistical analysis of fold change was performed over time. Our study concluded that all the seven selected metabolites were commonly involved in lipid metabolism and purine metabolism.
Highlights
Functional dyspepsia (FD) is defined as “a discomfort or pain in the upper part of the abdomen” [1]
A total of eight, nine, six, and seven candidates were searched for endogenous substances from human metabolome database (HMDB)
We have evaluated the changes in endogenous urinary metabolites after administration of DA-9701 (Corydalis tuber and Pharbitidis seed extract), through untargeted metabolomics approaches
Summary
Functional dyspepsia (FD) is defined as “a discomfort or pain in the upper part of the abdomen” [1]. A study on the Greek population confirmed that CD14, GNB3, MIF, and TRPV1 gene polymorphisms were related to a higher susceptibility of epigastric pain syndrome [3]. ~20% (n = 694) complained of dyspeptic symptoms such as epigastric pain or postprandial discomfort. A gastrointestinal prokinetic agent, was developed for the treatment of FD and has been widely used; severe arrhythmias, such as Torsades de pointes, have been reported as one of its side effects [6]. New prokinetic agents have been developed, they show side effects such as cardiac arrhythmia and some had failed to show enough efficacy [7]. There is a growing need to develop safer and more effective prokinetic agents
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